CLINICAL MICROBIOLOGY REVIEWS, Oktober 2002, hlm. 595–612 Vol. 15, No. 4 0893-8512 / 02 / $ 04.00 0 DOI: 10.1128 / CMR.15.4.

595–
612.2002
Hak Cipta © 2002, American Society for Microbiology. Seluruh hak cipta.

Sejarah Parasitologi Manusia

FEG Cox *
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical
Medicine, London WC1E 7HT, United Kingdom

PENDAHULUAN ..................... .................................................. .................................................. .................

............. 595 EVOLUSI MANUSIA, MIGRASI, PERADABAN, DAN INFEKSI PARASITIK ......... ...............
595 RECORDS AWAL
TERTULIS ............................... .................................................. ................................................ 596
PENEMUAN OF THE HELMINTH
WORMS .............................................. .................................................. ....... 596
Ascaris dan
Ascariasis ....................................... .................................................. ..................................................
596 Penyakit Cacing tambang dan Cacing
tambang ............................................. ..................................... .................................. 597 Trichinella
dan Trichinosis ............ .................................................. .................................................. ....................
597 Strongyloides dan
Strongyloidiasis .......................... .................................................. ............................................ 598
Dracunculus dan Dracunculiasis (Guinea Penyakit
Cacingan) ............................................... ................................ 598 Filarial Worms and Lymphatic
Filariasis (Elephantiasis) ......... .................................................. .................... 599 Loa dan Loiasis
(Cacing Mata) serta Onchocerca dan Onchocerciasis (Kebutaan Sungai) .............. ................... 599
Schistosomes dan
Schistosomiasis ........................... .................................................. .......................................... 600
Penyakit Cacing Hati dan
Paru .. .................................................. ............ .................................................. .......... 601 Cestodiasis
(Infeksi cacing pita) .................................. .................................................. .................................. 601
PENEMUAN PROTOZOA PARASITIK .......... .................................................. ..................................... 603
Amoebae dan
Amoebiasis ......... .................................................. .................................................. ......................... 603
Giardia dan
Giardiasis ..................... .................................................. .................................................. ..................
604 Trypanosomes Afrika dan Penyakit
Tidur .......................... .................................................. ........................ 604 Trypanosomiasis Amerika
Selatan: Penyakit Chagas .................. .................................................. ..................... 604 Leishmania
dan Leishmaniasis .. .................................................. .................................................. .......................
605
Malaria ......................... .................................................. .................................................. .........................
............... 606 Toksoplasma, Toksoplasmosis, dan Infeksi yang Disebabkan oleh Terkait
Organisme ................................................. .606
Mikrosporidia ............................................... .................................................. ...........................................
....... ... 607
RINGKASAN DAN
KESIMPULAN ........................................... .................................................. ............................. 608
UCAPAN TERIMA
KASIH ................... .................................................. .................................................. .................... 608
REFERENSI ............................ .................................................. ...... .................................................. ..........
............ 608

PENDAHULUAN daripada ini, dan pemahaman kita tentang parasit dan

Selama sejarah kita yang relatif singkat di Bumi, manusia
telah memperoleh parasit dalam jumlah yang luar biasa,
sekitar 300 spesies cacing cacing dan lebih dari 70 spesies
spesies protozoa (9). Banyak di antaranya adalah parasit
langka dan tidak disengaja, tetapi kami masih menyimpan
sekitar 90 spesies yang relatif umum, yang sebagian kecil
menyebabkan beberapa penyakit terpenting di dunia, tak
terhindarkan, inilah yang paling mendapat perhatian.
Karena sebagian besar penyakit parasit ini terjadi terutama
di daerah tropis, bidang parasitologi cenderung tumpang
tindih dengan bidang kedokteran tropis, dan dengan
demikian sejarah kedua bidang ini saling terkait. Namun,
ada lebih banyak hal dalam sejarah parasitologi manusia
infeksi parasit tidak dapat dipisahkan dari pengetahuan kita
tentang sejarah ras manusia. Secara khusus, penyebaran
dan penyebaran banyak parasit di seluruh dunia sebagian
besar disebabkan oleh aktivitas manusia, dan munculnya
AIDS telah menambah babak baru dalam sejarah
parasitologi.
* Alamat surat: Department of Infectious and Tropical Diseases,
London School of Hygiene and Tropical Medicine, London WC1E
7HT, United Kingdom. Telp: 44 (0) 20 7927 2614. Fax: 44 (0) 20
7580 9075. E-mail: frank.cox@lshtm.ac.uk.
595
EVOLUSI MANUSIA, MIGRASI, PERADABAN, DAN
INFEKSI PARASITIK
Evolusi manusia dan infeksi parasit telah berjalan seiring,
dan berkat spin-off dari Proyek Genom Manusia, kita
sekarang tahu lebih banyak tentang asal-usul ras manusia
daripada sebelumnya (197 ). Suatu saat, sekitar 150.000
tahun yang lalu, Homo sapiens muncul di Afrika timur (254)
dan menyebar ke seluruh dunia, kemungkinan dalam
beberapa gelombang (252), hingga 15.000 tahun yang lalu
pada akhir Zaman Es manusia telah bermigrasi dan
menghuni hampir seluruh dunia. di muka bumi, membawa
beberapa parasit bersama mereka dan mengumpulkan
parasit lainnya di jalan. Untuk keperluan review kali ini,
596 COX CLIN. MICROBIOL. REV.
mengakibatkan munculnya sejumlah infeksi parasit
oportunistik baru di seluruh dunia (5).
Kami mulai belajar banyak tentang riwayat infeksi parasit
di masa lalu dari studi artefak arkeologi, seperti keberadaan
telur cacing atau kista protozoa dalam koprolit (feses yang
membatu atau mengering) dan tubuh yang diawetkan
secara alami atau buatan; dari studi tersebut telah muncul
ilmu baru, paleoparasitologi. Contoh dari beberapa
penemuan ini akan dibahas nanti.
Begitu luas bidang parasitologi manusia, dan begitu
banyak penemuan yang dibuat, sehingga tidak mungkin
untuk berlaku adil terhadap keseluruhan subjek. Karena itu;
hanya aspek yang paling signifikan dan parasit terpenting
yang dipertimbangkan dalam dua judul utama, cacing
cacing dan pro tozoa.
CATATANTERTULIS AWAL
YANGCatatan tertulis pertama dari apa yang hampir pasti
infeksi para sitic berasal dari periode pengobatan Mesir dari
3000 hingga 400 SM, khususnya papirus Ebers tahun 1500
SM yang ditemukan di Thebes (29). Belakangan, ada
banyak penjelasan rinci tentang berbagai penyakit yang
mungkin atau tidak mungkin disebabkan oleh parasit,
khususnya demam, dalam tulisan-tulisan para dokter
Yunani antara 800 hingga 300 SM, seperti kumpulan karya
Hippocrates, yang dikenal sebagai Corpus Hippocratorum,
dan dari tabib dari peradaban lain termasuk Cina dari 3000
hingga 300 SM, India dari 2500 hingga 200 SM, Roma dari
700 SM hingga 400 M, dan Kekaisaran Arab pada paruh
akhir milenium pertama. Seiring waktu berlalu, deskripsi
infeksi menjadi lebih akurat dan dokter Arab, khususnya
Rhazes (850 hingga 923 M) (226) dan Ibnu Sina (980
hingga 1037 M) (11), menulis karya medis penting yang
berisi banyak informasi. tentang penyakit yang jelas
disebabkan oleh parasit.
Di Eropa, Abad Kegelapan dan Pertengahan, yang
dicirikan oleh kepercayaan religius dan takhayul, menahan
kemajuan medis sampai Renaisans, yang melepaskan
kesibukan yang akhirnya mengarah pada penemuan besar
yang menandai akhir abad ke-19 dan awal abad ke-19.
Tanggal 20. Penemuan ini termasuk pembongkaran teori
generasi spontan dan evolusi teori kuman oleh Louis
Pasteur, demonstrasi oleh Pasteur bahwa penyakit dapat
disebabkan oleh bakteri, penemuan virus oleh Pierre-Paul
Emile Roux, pengantar oleh Robert Koch metode
pencegahan penyakit yang disebabkan oleh
mikroorganisme, dan inasi vektor oleh Patrick Manson
dalam penularan parasit. Tokoh-tokoh hebat pada periode
parasit yang menginfeksi manusia dapat diklasifikasikan
sebagai pusaka atau suvenir. Pusaka adalah parasit yang
diwarisi dari nenek moyang kita di Afrika, dan suvenir
adalah yang kita peroleh dari hewan yang berhubungan
dengan kita selama evolusi, migrasi, dan praktik pertanian
kita. Perkembangan pemukiman dan kota memfasilitasi
penularan infeksi antar manusia, dan terbukanya jalur
perdagangan mengakibatkan penyebaran infeksi parasit
yang lebih luas. Perdagangan budak, yang berkembang
selama tiga setengah abad dari sekitar 1500, membawa
parasit baru ke Dunia Baru dari Dunia Lama (58);
Belakangan ini, penyebaran virus human immunodeficiency
HIV dan AIDS dan imunodepresi yang terkait dengan
kondisi ini memiliki
ini membuat penemuan di sejumlah bidang, dan temuan
serta ide mereka saling bertumpu. Nama Pasteur, Koch,
Roux, dan Manson muncul berkali-kali dalam sejarah
parasitologi dan mikrobiologi.
PENEMUAN CACAT HELMINTH
Karena ukuran besar beberapa cacing, seperti cacing
gelang Ascaris dan cacing pita, hampir pasti nenek moyang
kita yang paling awal pasti telah menyadari cacing umum
ini. Ada beberapa bukti untuk asumsi ini berdasarkan studi
kontemporer tentang suku-suku primitif di Sarawak dan
Kalimantan Utara, di mana Hoeppli menemukan bahwa
kebanyakan orang
sadar akan cacing gelang dan cacing pita usus mereka
(120, 121). Beberapa sejarawan telah mengidentifikasi
referensi tentang cacing cacing dan penyakitnya di dalam
Alkitab, tetapi bagian yang relevan terbuka untuk beberapa
interpretasi. Di antara papirus medis Mesir, papirus Ebers
mengacu pada cacing usus, dan catatan ini dapat
dikonfirmasi dengan penemuan telur cacing yang
terkalsifikasi pada mumi yang berasal dari 1200 SM. Orang
Yunani, khususnya Hippocrates (460 hingga 375 SM) (131),
tahu tentang cacing dari ikan, hewan peliharaan, dan
manusia. Dokter Romawi termasuk Celsus (25 SM hingga
50 M) (244) dan Galen (Galenus dari Pergamon, 129
hingga 200 M) (147) akrab dengan cacing gelang manusia
Ascaris lumbricoides dan Entero bius vermicularis dan
cacing pita yang termasuk dalam genus Tae nia. Beberapa
saat kemudian, Paulus Aegineta (625 hingga 690 M)
dengan jelas menggambarkan Ascaris, Enterobius, dan
cacing pita dan memberikan gambaran klinis yang baik
tentang infeksi yang mereka sebabkan (105). Menyusul
kemunduran Kekaisaran Romawi, studi tentang pengobatan
beralih ke dokter Arab, termasuk Ibnu Sina, yang tidak
hanya mengenali Ascaris, Enterobius, dan cacing pita tetapi
juga cacing guinea, Dracunculus medinensis, yang telah
tercatat di beberapa bagian Arab. dunia, khususnya di
sekitar Laut Merah, selama lebih dari 1.000 tahun.
Literatur medis Abad Pertengahan sangat terbatas, tetapi
ada banyak referensi tentang cacing parasit. Dalam
beberapa kasus, mereka dikenali sebagai kemungkinan
penyebab penyakit tetapi secara umum, tulisan-tulisan pada
periode tersebut mencerminkan budaya, kepercayaan, dan
ketidaktahuan pada saat itu. Ilmu helminthol ogy benar-
benar berkembang pesat pada abad ke-17 dan ke-18
setelah munculnya kembali ilmu pengetahuan dan keilmuan
pada masa Renais. Linnaeus menggambarkan dan
menamai enam cacing cacing, Ascaris lumbricoides,
 Ascaris vermicularis ( Enterobius vermicularis), Gordius
medinensis ( Dracunculus medinensis), Fasciola hepatica,
Taenia solium, dan Taenia lata ( Diphyllo bothrium latum)
(160). Setelah itu, lebih banyak spesies dideskripsikan
hingga pada awal abad ke-20, 28 spesies telah dicatat pada
manusia, jumlah yang sekarang telah berkembang menjadi
sekitar 300 spesies, termasuk catatan kebetulan dan sangat
langka (46). Bahkan jika beberapa di antaranya meragukan,
setidaknya 280 spesies dikenali oleh Ashford dan Crewe
dalam daftar periksa beranotasi mereka (9).
Ascaris dan Ascariasis
Ascaris lumbricoides, cacing gelang besar, adalah satu
dari enam cacing yang terdaftar dan diberi nama oleh
Linnaeus; namanya tetap tidak berubah sejak saat itu.
VOL. 15, 2002 SEJARAH PARASITOLOGI MANUSIA 597
1368 dan 1644 (59). Keberadaan cacing besar yang
panjangnya mencapai 15 sampai 35 cm dan sering buang
air dalam tinja atau kadang keluar dari anus ini sangat
terlihat jelas. Ada banyak catatan tertulis termasuk papirus
medis Mesir, karya Hippocrates pada abad kelima SM,
tulisan Chi nese dari abad kedua dan ketiga SM (121), dan
teks dokter Romawi dan Arab (105). Anehnya, baru pada
akhir abad ke-17 anatomi rinci cacing tersebut dijelaskan,
pertama oleh Edward Tyson, seorang dokter Inggris (258),
dan tak lama kemudian oleh Francesco Redi Italia, yang
menggambarkan cacing dalam bukunya Osservazioni In
torno Agli Animali Viventi che si Trovano Negli Animali
Viventi, salah satu buku pertama tentang parasitologi (223).
Kedua publikasi ini, bersama dengan publikasi Tyson pada
cacing pita hu mans (257), dapat dianggap menandai awal
subdisiplin helminthology, yang mencapai puncaknya pada
abad ke-19. Selama periode ini pula upaya nyata pertama
dilakukan untuk memahami infeksi yang disebabkan oleh
Ascaris dan cacing lain dan bagaimana mereka dapat
diobati (72, 105). Sementara itu, masalah bagi mereka yang
mempelajari Ascaris dan nematoda parasit lainnya adalah
bagaimana telur parasit menginfeksi inang baru setelah
meninggalkan inang aslinya. Baru pada tahun 1862
penularan dengan menelan telur dilakukan oleh ilmuwan
medis Prancis Casimir Joseph Davaine (54, 136) dan
kemudian oleh ilmuwan Italia Giovanni Battista Grassi, yang
menginfeksi dirinya sendiri dengan telur A. lum bricoides
dan kemudian ditemukan telur di kotorannya (102). Siklus
hidup pada manusia, termasuk migrasi tahap larva di sekitar
tubuh, baru ditemukan pada tahun 1922 oleh seorang
dokter anak Jepang, Shimesu Koino, yang menginfeksi baik
seorang sukarelawan maupun dirinya sendiri dan menyadari
apa yang terjadi ketika ia menemukan sejumlah besar larva
di dahinya (136, 141). Ada catatan bagus tentang sejarah
ascariasis by Grove (105) dan Goodwin (100).
Cacing tambang dan Penyakit Cacing
tambang Infeksi cacing tambang pada manusia
disebabkan oleh dua spesies, Ancylostoma duodenale dan
Necator americanus, yang pertama berasal dari Asia dan
yang terakhir berasal dari Afrika. Siklus hidup kedua cacing
tersebut serupa. Cacing jantan dan betina dewasa hidup di
usus kecil, di mana dapat menyebabkan kehilangan darah
dalam jumlah besar. Telur keluar bersama tinja untuk
mencemari tanah, di mana larva muncul dan berganti kulit
menjadi larva infeksius yang masuk melalui kulit inang baru.
Diperkirakan satu miliar orang terinfeksi cacing ini. Cacing
dewasa hidup di dalam usus, dan betina menghasilkan telur
yang keluar bersama tinja, dan larva di dalam telur
berkembang ke tahap infektif di tanah. Manusia menjadi
terinfeksi ketika makanan yang terkontaminasi telur infektif
dimakan dan larva muncul di usus. Cacing tidak segera
matang tetapi bermigrasi ke seluruh tubuh, mencapai paru-
paru, dari mana mereka dibatukkan dan ditelan dan
kemudian berkembang menjadi dewasa di usus. Karena
cariasis adalah infeksi purba, dan A. lumbricoides telurtelah
ditemukan pada koprolit manusia dari Peru yang berasal
dari tahun 2277 SM (123, 213) dan Brazil dari sekitar 1660
hingga 1420 SM (82, 83). Di Dunia Lama, ada catatan A.
lumbricoides di mumi Mesir Kerajaan Tengah yang berasal
dari tahun 1938 sampai 1600 SM (45) dan dari Cina pada
Dinasti Ming antara AD
Pada manusia, larva bermigrasi ke paru-paru dan trakea,
dari situ mereka ditelan sebelum menjadi dewasa di usus
kecil. Infeksi cacing tambang manusia Hu telah dikaitkan
dengan manusia di Dunia Lama selama lebih dari 5.000
tahun (121). Adanya infeksi cacing tambang di Amerika pra-
Columbus adalah topik yang sangat diperdebatkan. Robert
Desowitz memiliki sedikit keraguan bahwa cacing kait ada
sebelum kedatangan orang Eropa (57), tetapi Kathleen
Fuller menyatakan bahwa cacing tambang diperkenalkan ke
Amerika setelah tahun 1492 (93). Bukti paleoparasitologis
tampaknya mendukung gagasan Desowitz
sejakdiidentifikasi sebagai sel telurAncy lostoma sp. telah
ditemukan dalam koprolit manusia yang berasal dari suatu
tempat antara 3350 SM dan 480 M (84). Larval nema todes,
kemungkinan cacing tambang, telah ditemukan dalam
sampel tinja sekitar 200 SM dari Dataran Tinggi Colorado
(79).
Pengenalancacing tambang ke Amerika dibahas secara
rinci di tempat lain yang lebih (81, 114, 115, 123).
Tanda klasik penyakit cacing tambang adalah anemia,
pucat kuning kehijauan, dan lesu. Tak satu pun dari gejala
ini jelas atau tidak ambigu, dan satu ciri khas yang
ditunjukkan oleh beberapa individu, geofagi, tidak selalu
terkait dengan penyakit. Meskipun cacing pasti ada di
banyak peradaban, kebanyakan infeksi tidak diketahui
sehingga laporan awal penyakit yang ditafsirkan dalam
retrospeksi harus ditangani dengan hati-hati. Pucat
kehijauan yang disebut Egyptian tian chlorosis, pertama kali
dikaitkan dengan infeksi cacing tambang oleh para ilmuwan
abad ke-19, tidak dicatat dalam papirus Mesir awal. Telah
dikemukakan bahwa kondisi misterius aaa yang terjadi di
banyak papirus termasuk papirus Ebers mungkin merujuk
pada cacing tambang (69), tetapi tidak ada bukti nyata
untuk ini (205). Hal ini dibahas ketika mempertimbangkan
schistosomi asis di bawah ini. Ada referensi untuk pucat
kekuningan dan geoph agy dalam karya Hippocrates dan
Lucretius, yang mencatat pucat yang terlihat pada
penambang sekitar 50 SM. Ada juga referensi dari abad
ketiga SM di Cina untuk kemalasan dan penyakit kuning
(121). Selama abad ke-18 dan 19, terjadi peningkatan
jumlah rekaman dari Hindia Barat dan Amerika Selatan dan
Tengah (105). Cacing ditemukan pada manusia pada tahun
1838 oleh dokter Italia Angelo Dubini (67, 136), dan
hubungan antara cacing dan penyakit akhirnya ditemukan
oleh Wilhelm Griesinger pada tahun 1854 (104, 136).
Meskipun hubungan antara pucat dan bekerja di tambang
telah dibuat oleh Lucretius, baru pada tahun 1879 dokter
hewan Italia Edoardo Perroncito membuat hubungan yang
 nyata saat menyelidiki penyakit penambang di terowongan
St. Gothard (215). Kondisi di tambang mendukung
perkembangan larva cacing tambang yang membutuhkan
kehangatan dan kelembapan. Fakta bahwa larva cacing
tambang masuk ke dalam tubuh dengan cara mengebor
melalui kulit tidak ditemukan sampai akhir abad ke-19,
ketika Arthur Looss secara tidak sengaja menginfeksi
dirinya sendiri (136, 161). Pada awal abad ke-20, penyakit
cacing tambang merupakan masalah yang sangat serius di
Amerika Serikat sehingga Rockefeller Foundation
mengambil tugas untuk mengendalikan penyakit tersebut,
suatu kegiatan yang kemudian mengarah pada
pembentukan sejumlah Sekolah Kesehatan Masyarakat dan
pembentukan Organisasi Kesehatan Dunia (73). Ada
catatan bagus tentang sejarah penyakit cacing tambang
oleh Ball (13), Foster (89), dan Grove (105).
598 COX CLIN. MICROBIOL. REV.
Rumah Sakit tholomew di London dan kemudian diberi
gelar kebangsawanan sebagai dokter yang sangat
terhormat, tetapi laporan definitif ditulis oleh Richard Owen,
yang mengecilkan peran Paget (211) dan tidak menyadari
bahwa cacing di otot manusia adalah tahap larva
nematoda. Cacing dewasa ditemukan oleh Rudolf Virchow
pada tahun 1859 (266) dan Friedrich Zenker pada tahun
1860, dan Zenkerlah yang akhirnya mengenali signifikansi
klinis dari infeksi tersebut dan menyimpulkan bahwa
manusia terinfeksi dengan memakan daging babi mentah
(136, 281). Pentingnya studi ini tidak hanya terletak di
bidang parasitologi manusia tetapi juga di bidang
parasitologi yang lebih umum yang berkaitan dengan
penularan parasit antara spesies hewan yang berbeda dan
pentingnya hubungan predator-mangsa dalam penularan
tersebut. Ada catatan bagus tentang sejarah trikinosis oleh
Bundy dan Michael (31), Foster (89), dan Grove (105).
Strongyloides dan Strongyloidiasis
Manusia merupakan inang dari dua spesies
Strongyloides, S. sterco ralis dan S. fuelleborni, yang mana
terdapat dua subspesies, S. f. fuelleborni di Afrika dan S. f.
kellyi di Papua Nugini. Sejauh menyangkut penyakit
manusia, S. stercoralis adalah spesies yang lebih umum
dan penting. Siklus hidupnya lebih kompleks daripada siklus
nematoda lain yang telah dibahas sejauh ini dan melibatkan
generasi parasit dan yang hidup bebas. Cacing betina
paritogenik dewasa di usus halus bertelur yang menetas di
dalam inang untuk menghasilkan larva tahap pertama, yang
dikeluarkan melalui tinja dan hidup bebas di dalam tanah. Di
sini mereka berganti kulit untuk menghasilkan larva infektif
yang menembus kulit dan dibawa ke seluruh tubuh ke paru-
paru dan ditelan serta mencapai usus dengan cara yang
sama seperti cacing tambang. Kadang-kadang larva
menjadi dewasa sampai tahap infektif dalam tinja di kulit
dan menginfeksi kembali inang melalui kulit (autoinfeksi),
atau larva bisa matang sampai tahap infektif tanpa
meninggalkan usus dan menembus dinding usus. Setelah
itu, dalam kedua kasus, infeksi berlanjut seperti yang
dijelaskan di atas. Pada individu yang mengalami
imunosupresan, stadium larva dapat ditemukan di seluruh
organ dalam. S. stercoralis juga memiliki alternatif siklus
hidup bebas di dalam tanah. Mengingat tidak adanya telur
dan ukuran kecil dari larva, ditambah dengan kebingungan
dengan spesies nematoda hidup bebas lainnya, tidak
mengherankan bahwa S. stercoralis tidak dikenali sampai
Trichinella dan Trichinosis
Trichinosis, juga dikenal sebagai infeksi trichinellosis dan
trichina, disebabkan oleh cacing nematoda usus Trichinella
spiralis, yang membutuhkan dua inang dalam siklus
hidupnya. Cacing betina menghasilkan larva yang
menempel di otot, dan inang baru terinfeksi saat otot
dimakan. Karena infeksi manusia biasanya didapat dengan
memakan daging babi yang terinfeksi larva encysted, ini
mungkin telah memunculkan tradisi Mosaic dan Islam untuk
menghindari babi, sebuah praktik yang juga dikaitkan
dengan infeksi cacing pita (lihat di bawah). Hubungan
antara infeksi trichina dan babi telah lama dikenal, tetapi
larva encysted di otot tidak terlihat sampai tahun 1821 dan
bahkan kemudian tidak terkait dengan penyakit pada
manusia (253). Penemuan cacing pada manusia pada
tahun 1835 dilakukan oleh James Paget, seorang
mahasiswa kedokteran di St. Bar
tahun 1876, ketika larva dan penyakit yang kuat loidiasis
keduanya ditemukan oleh Louis Alexis Normand, seorang
dokter di rumah sakit angkatan laut Prancis di Toulon (105).
Tak lama kemudian ditemukan cacing dewasa dan, tidak
tahu apa itu, mengirim mereka ke Profesor Arthur Re´ne´
Jean Baptiste Bavay di French Conseil Supe´rieur de Sante
´, yang menyadari bahwa mereka adalah cacing dewasa
dari larva yang ditemukan di kotoran (15). Pada tahun 1883,
ahli parasitologi Jerman Karl Georg Friedrich Rudolf
Leuckart menemukan pergantian generasi yang melibatkan
fase parasit dan kehidupan bebas (157). Penemuan bahwa
infeksi terjadi melalui kulit dibuat oleh seorang dokter
Belgia, Paul Van Durme, yang penelitiannya didasarkan
pada penelitian Looss, yang disebutkan di atas, yang telah
menunjukkan bahwa A. duodenale menginfeksi inangnya
dengan cara ini (262). Sekarang diperkirakan bahwa Van
Durme mungkin bekerja dengan A. fuelleborni (105), tetapi
cara infeksi yang benar telah ditetapkan, dan Looss-lah
yang kemudian berhasil menginfeksi dirinya dengan
meletakkan larva S. stercoralis di kulitnya dan menemukan
larva dalam kotorannya 64 hari kemudian (162). Friedrich
Fu¨lleborn, bekerja dengan anjing di Hamburg,
menggambarkan fenomena autoinfeksi dan menemukan
bagaimana S. stercoralis (dan juga Ancylostoma spp.)
Bermigrasi ke seluruh tubuh sebelum berakhir di usus (92,
136). Selama lebih dari setengah abad, S. stercoralis
menerima sedikit perhatian sampai studi rinci tentang
infeksi pada tawanan perang yang telah tertular infeksi
mereka di Timur Jauh pada 1940-an mengungkapkan
infeksi yang menyebar pada pasien yang mengalami
imunosupresi (97). Kemudian ditemukan bahwa
Strongloides infeksilebih parah pada pasien yang terinfeksi
dengan human T-lymphotropic virus tipe 1 dan pernah,
tetapi tidak lagi, dianggap sebagai penyebab utama AIDS
(5, 111). Strongyloides Infeksidan Strongyloidiasis tidak
tercakup dengan baik dalam literatur, tetapi ada penjelasan
yang baik oleh Grove (105).
Dracunculus dan Dracunculiasis (Guinea Worm
Disease) Penyakit
parasit yang terdokumentasi paling baik yang diketahui
dari masa awal telinga tidak diragukan lagi disebabkan oleh
cacing nematoda Dracunculus medinensis. Cacing dewasa
hidup di jaringan ikat subkutan, dari mana cacing betina
muncul untuk melepaskan ribuan larva ke dalam air, di
mana mereka dimakan oleh inang perantara, krustasea
 siklopodid, di mana mereka berkembang menjadi larva
infektif yang menginfeksi manusia ketika krusta berhenti
secara tidak sengaja ditelan dengan air minum. Cacing
betina besar, panjangnya hingga 80 cm, menonjol dari kulit,
biasanya dari kaki, dan menyebabkan peradangan dan
iritasi yang hebat, tanda-tanda yang sangat tidak biasa dan
tidak ambigu sehingga teks kuno dapat ditafsirkan dengan
pasti. Telinga deskripsi liest adalah dari papirus Ebers dari
1500 SM dan termasuk petunjuk untuk mengobati aat
pembengkakan pada tungkai; tampaknya merujuk pada
sifat infeksi dan teknik menghilangkan cacing. Penafsiran ini
diterima secara luas oleh sebagian besar ahli parasitologi
(89, 105, 121, 251), tetapi terdapat kesulitan dalam
menafsirkan teks khusus ini karena kata aat dapat berarti
pembengkakan (205). Namun demikian, konfirmasi
keberadaan cacing ini di Mesir kuno berasal dari
ditemukannya cacing betina yang diawetkan dengan baik
dan cacing kalsifikasi pada mumi Mesir (205).
Dracunculiasis adalah salah satu dari sedikit penyakit
yang secara jelas dijelaskan dalam Alkitab, dan sebagian
besar parasitolog menerima bahwa "ular berapi-api" yang
VOL. 15, 2002 SEJARAH PARASITOLOGI MANUSIA 599
Ketertarikan pada dracunculiasis muncul kembali ketika
kondisi tersebut dikenali oleh wisatawan Eropa yang
mengunjungi Afrika (karena itu nama umum, cacing Guinea)
dan Asia. Pada tahun 1674, Georgius Hieronymus
Velschius memprakarsai penelitian ilmiah tentang cacing
dan penyakit yang ditimbulkannya (263), dan pada tahun
1819, Carl Asmund Rudolphi menemukan cacing betina
dewasa yang mengandung larva (234), sebuah penemuan
yang ditindaklanjuti pada tahun 1834 oleh seorang
Denmark. dikenal hanya sebagai Jacobson (128). Pada
tahun 1836, D. Forbes, seorang perwira tentara Inggris
yang bertugas di India, menemukan dan menggambarkan
larva D. medinensis di dalam air (87), dan selama beberapa
tahun berikutnya beberapa ahli parasitologi, termasuk
George Busk (33), mengejar gagasan tersebut bahwa
manusia terinfeksi melalui kulit. Baru pada tahun 1870
seluruh siklus hidup, termasuk tahapan dalam inang
perantara krustasea, diuraikan oleh Alekej Pavlovitch
Fedchenko (80, 136) dari Rusia. Pengamatan Fedchenko
mendapat penerimaan luas setelah dikonfirmasi oleh
Manson pada tahun 1894 (179), dan seluruh siklus hidup
akhirnya diuraikan pada tahun 1913 oleh ahli bakteriologi
India Dyneshvar At maran Turkhud, yang berhasil
menginfeksi sukarelawan manusia denganterinfeksi
Cyclops yang (136, 256) . Ada catatan yang lebih rinci
tentang sejarah Dracunculus oleh Foster (89), Grove (105),
dan Tayeh (251).
Cacing Filaria dan Filariasis Limfatik (Kaki gajah)
Filariasis limfatik disebabkan oleh infeksi cacing
nematoda Wuchereria bancrofti, Brugia malayi, dan B.
timori, yang ditularkan oleh nyamuk. Penemuan siklus hidup
oleh Patrick Manson pada tahun 1877 dianggap sebagai
salah satu penemuan paling signifikan dalam pengobatan
tropis, tetapi dalam konteks sejarah parasitologi, hal itu
lebih baik dianggap sebagai perpanjangan logis dari banyak
hal yang telah terjadi sebelumnya. Seperti Dracunculus,
cacing filaria dewasa hidup di jaringan subkutan, tetapi tidak
seperti Dracunculus, larva, yang disebut mikrofilaria,
diproduksi oleh cacing betina masuk ke dalam darah dan
diambil oleh nyamuk penghisap darah saat makan. Setelah
menimpa orang Israel di wilayah Laut Merah setelah
Eksodus dari Mesir sekitar 1250 hingga 1200 SM
sebenarnya adalah cacing Guinea (16). Penafsiran paling
otoritatif dari teks alkitabiah ini, yang diperkirakan telah
ditulis pada abad kedelapan SM, adalah bahwa oleh Gottlob
Friedrich Heinrich Ku¨chenmeister, seorang ahli
parasitologi, teolog, dan sarjana Ibrani, dalam buku teks
tahun 1855 yang diterjemahkan ke dalam bahasa Inggris
sebagai Hewan dan Parasit Sayuran (144). Teks Asiria di
perpustakaan Raja Ashurbanipal dari abad ke-7 SM juga
merujuk pada kondisi yang jelas dracunculiasis, dan
deskripsi selanjutnya tentang dracunculiasis terjadi di
semua teks utama Yunani dan Romawi dan karya para
tabib Arab abad ke-10 dan ke-11 (105, 121). Karena ada
referensi ke "Medina vein" dalam literatur Arab, beberapa
sejarawan berpendapat bahwa tabib Arab mungkin mengira
bahwa cacing itu sebenarnya adalah pembuluh darah yang
busuk, tetapi sebagian besar pengamat yang terinformasi
sekarang setuju bahwa para tabib Arab sepenuhnya
menyadari cacing tersebut. sifat mirip dracunculiasis tetapi
belum tentu penyebab sebenarnya dari penyakit ini (105,
251).
berkembang pada nyamuk, mikrofilaria disuntikkan ke inang
baru saat nyamuk makan lagi. Salah satu bentuk penyakit
yang pasti menarik perhatian nenek moyang kita adalah ele
phantiasis, yang ditandai dengan pembengkakan anggota
badan, payudara, dan alat kelamin yang aneh. Kelainan
bentuk ini tampaknya telah dideskripsikan dan digambarkan
dalam gambar sejak masa paling awal, tetapi penafsiran
catatan awal harus dilihat dengan hati-hati (199). Filariasis
limfatik pernah, dan, umum terjadi di sepanjang Sungai Nil
dan, meskipun tidak ada catatan tertulis, bagian tubuh yang
bengkak dari patung Firaun Mesir Mentuhotep II dari sekitar
2000 SM menunjukkan bahwa ia menderita penyakit kaki
gajah, dan patung kecil serta emas Bobot dari budaya Nok
di Afrika Barat dari sekitar tahun 500 M menggambarkan
karakteristik scrota dari kaki gajah yang membesar (199).
Penulis Yunani dan Romawi mengetahui diagnosis banding
dari kondisi tersebut dan menggunakan istilah
"elephantiasis graecorum" untuk menggambarkan kusta
dan istilah "elephantiasis arabum" untuk menggambarkan
filariasis limfatik; dokter Arab, termasuk Ibnu Sina, juga
menyadari perbedaan antara lepra dan limfatik filariasis
(137). Laporan definitif pertama dari filariasis limfatik baru
mulai muncul pada abad ke-16. Lymphatic filariasis is also
known as “the curse of St. Thomas” (151), and on a visit to
Goa between 1588 and 1592, the Dutch explorer Jan
Huygen Linschoten recorded that the
descendants of those that killed St. Thomas were “all born
with one of their legs and one foot from the knee
downwards as thick as an elephants leg” (32). Thereafter,
there are numerous references to elephantiasis, especially
in Africa but also in Asia, including China, where Manson
was later to discover the life cycle of the parasite. Another
pathological condition asso ciated with lymphatic filariasis is
chyluria, in which the urine appears milky. This condition
was recorded by William Prout in his 1849 book On the
Nature and Treatment of Stomach and Renal Diseases
(219).
The larval microfilariae were first seen in hydroceel fluid
by the French surgeon Jean-Nicolas Demarquay in 1863
(55, 136) and, independently, in urine by Otto Henry
Wucherer in Brazil in 1866 (136, 280). It remained for
Timothy Lewis, a Scottish physician working in Calcutta, to
 confirm the finding of micro filariae in urine and blood and to
recognize their significance in elephantiasis (136, 159). The
adult worm was described by Joseph Bancroft in 1876 (14,
136) and named Filaria bancrofti in his honour by the British
helminthologist Thomas Spencer Cobbold (44). The
elucidation of the life cycle, one of the triumphs of
parasitological research, was the work of Patrick Manson in
1877 (174). This is widely regarded as the most significant
discovery in tropical medicine, with implications that went far
beyond helminthology into such diverse areas as malaria
and the arboviruses. The story of Manson's discoveries has
been told many times (43, 44, 70, 89, 105, 182, 199, 240),
but what is often omitted from the history of Manson's
discov eries is the fact that he was aware of Fedchenko's
earlier studies on the life cycle of D. medinensis and its
transmission using an intermediate cyclopodid host (see
above). Fedchen ko's observations stimulated Manson to
seek an intermediate host but also led him astray when he
tried to demonstrate that infection was caused by drinking
contaminated water. Manson, then working in Amoy in
China, found microfilariae in the blood of dogs and humans
and hypothesized that these para sites in the blood might be
transmitted by blood-sucking in sects. Accordingly, he fed
mosquitoes on the blood of his gardener, who was
600 COX CLIN. MICROBIOL. REV.
are no reliable early records. In loiasis the adult worm
moves across the eye under the conjunctiva, an alarming
experience that must have attracted attention of both
sufferers and ob servers. An engraving by J. and T. de Bry
made in 1598 was at one time thought to depict the
extraction of a worm from the eye, but this has been hotly
disputed, and it is now thought that this particular engraving
represents a punishment for some offense rather than a
treatment (106). The first definitive record is that of a French
surgeon, Mongin, who, in 1770, described the worm
passing across the eye of a woman in Santa Domingo, in
the Caribbean, and recounts how he tried unsuc cessfully to
remove it (136, 190). There are, however, less detailed
earlier records of similar cases in 1768 and 1777 in an
account of the history of French Guyane and Cayenne by
Bertrand Bajon (12). In 1778, a French ship's surgeon, Fran
cois Guyot, noticed that slaves in transit from West Africa to
America suffered from recurrent ophthalmia and
successfully removed a worm from one of them (124). The
first English account of the removal of worms from the eye
is that by William Loney in 1848; thereafter, there are
increasing num bers of similar records (105). The
microfilariae were discov ered in 1890 by the
ophthalmologist Stephen McKenzie and were sent for
identification to Patrick Manson, who speculated that these
might be the larvae of Loa loa (176). Loa infections are not
confined to the eye, and there are also sometimes swellings
on the arms and legs caused by the worm in its wanderings.
These swellings, now known as Calabar swellings, were
first recorded by a Scottish ophthalmic surgeon, Douglas
Argyll-Robertson, in Old Calabar in Nigeria in 1895 (7), but
it was not until 1910 that Manson suggested that they might
be associated with infections by Loa loa (181), an opinion
shared by his colleague George Low (165). The
transmission by biting flies, Chrysops spp., was unraveled
by the British helmintholo gist Robert Thompson Leiper in
1912 (153). There is an ex cellent account of Loa and loasis
by Grove (105).
harboring the parasites, and found larval stages in the
mosquitoes (174). However, Manson thought that the
parasite escaped from the mosquito into water and that
humans acquired infection from this contaminated water by
drinking the parasi water or via penetration of the skin. The
actual mode of transmission was not established until
sugges tions made by the Australian parasitologist Thomas
Bancroft were followed up by Manson's assistant George
Carmichael Low, who demonstrated the presence of
microfilariae in the mouthparts of mosquitoes in 1900 (136,
164). The history of lymphatic filariasis is well described in
the works already cited in this section (43, 44, 70, 89, 105,
182, 199, 240).
Loa and Loiasis (Eye Worm) and Onchocerca
and Onchocerciasis (River Blindness)
Both loiasis, caused by infection with Loa loa, and
onchocer ciasis, caused by infection with Onchocerca
volvulus, are filarial worms with life cycles similar to those
described above. It is logical to consider these two
conditions together because both affect the eyes and must
have attracted the attention of early observers interested in
sight and blindness. Surprisingly, there
Onchocerciasis, caused by the filarial worm Onchocerca
vol vulus, is found mainly in Africa and in parts of South
America and the Arabian peninsula, where it was introduced
from Af rica, and it was only when these regions were
opened up by explorers that the disease was recognized.
The most important signs are blindness, an unexceptional
condition that might have been due to a number of causes,
and scaly, itchy, nodular skin, which was unusual and was
known locally in West Africa as kru kru or craw craw. The
microfilariae live in the skin and were discovered by the Irish
naval surgeon John O'Neill when ex amining skin snips from
patients suffering from craw craw in Ghana in 1874 (136,
208). Some years later, in 1890, the adult worms were also
discovered and identified by Patrick Manson (177). The role
of the microfilariae in causing the skin lesions was
established by Jean Montpellier and A. Lacroix in 1920
(191), and the part played by microfilaria in blindness was
finally elaborated by Jean Hissette in the Belgian Congo
(now the Democratic Republic of the Congo) in 1932 (117).
O. volvulus is transmitted by sandflies, and their role in the
trans mission of onchocerciasis was discovered by the
Scottish par asitologist Breadablane Blacklock in Sierra
Leone in the mid 1920s (19). There are accounts of the
history of onchocerciasis by Grove (105) and Muller (192).
Schistosomes and Schistosomiasis
Schistosomiasis, also known as bilharzia, is caused by
infec tion with trematode worms belonging to the genus
Schisto soma, of which the most important are S.
haematobium, S. mansoni, and S. japonicum. The adult
worms live in blood vessels associated with the intestine or
bladder, and the fe males produce eggs that are passed out
with the feces or urine. Larval stages, miracidia, emerge
from the eggs when they reach water and bore into the
intermediate host, a snail. After a period of multiplication in
the snail, the next larval stages, the cercariae, emerge, and
these are the stages that infect humans. The cercariae bore
through the skin and transform into schis tosomula that
 migrate through the body until they reach their final position
in blood, vessels where they mature. The patho logical
effects of the disease are due mainly to immunological
reactions to eggs that, instead of passing to the outside
world, become deposited in different tissues; the effects
depend on the tissues involved (111). In this context, it is
interesting that schistosomiasis has been associated with
carcinomas of the colon and bladder (111), one of the few
examples of parasitic infections causing cancer (the others
being the fluke infections opisthorchiasis and clonorchiasis
[see below]). There is nothing special about the symptoms
of schistosomiasis that might have attracted the attention of
early observers except the bloody urine, hematuria,
associated with S. haematobium infections, which is
discussed below. There is no doubt that schistosomi asis is
an ancient disease. In 1910, Marc Armand Ruffer found S.
haematobium eggs in two Egyptian mummies dating from
the 20th dynasty, 1250 to 1000 BC (235), a finding that is
generally regarded as the beginning of the subdiscipline of
palaeoparasitology. Thus, there is direct evidence that
schisto somes were present in ancient Egypt, and there
have been numerous attempts to find descriptions of this
condition in the medical papyri (3, 121, 122). The most
contentious word is aaa, which occurs in over 50 early
papyri including the Ebers pa pyrus. In some medical papyri
aaa occurs together with the initial hieroglyph suggesting a
VOL. 15, 2002 HISTORY OF HUMAN PARASITOLOGY 601
tinual and very abundant sweats diminished quantity of
urine- . . .becoming thick and bloody” (225). Thereafter
there are numerous reports of illnesses characterized by
hematuria, par ticularly among armies including those
involved in the Boer War (1899 to 1902). The worm S.
haematobium was described by the German parasitologists
Theodor Bilharz and Carl The odor Ernst von Siebold in
1851 (18, 136). Bilharz, with Wil helm Griesinger, made the
connection with the urinary disease a year later (17, 136).
Although it was known that other flukes employed a snail
vector, the search for the intermediate stages in the life
cycle of S. haematobium took a long time and a number of
experienced parasitologists including Arthur Looss,
Prospero Sonsino, and Thomas Cobbold, working at the
end of the 19th century, all failed to infect snails (105); it
was not until 1915 that Robert Leiper demonstrated the
complete life cycle in the snail host (154).
Our knowledge of the history of intestinal schistosomiasis
caused by S. mansoni dates back to conclusions reached
by Manson in 1902 that there were two species of
Schistosoma in humans (136, 180). Even though there had
been similar sug gestions by other workers, Manson's ideas
were not universally accepted, and it was Leiper who firmly
established the exis tence of S. mansoni as a separate
species in 1915 (153).
The third important species is the Asian form, S.
japonicum. One aspect of schistosomiasis japonica is
Katayama disease, an ancient disease that was properly
recorded in Japan in the Kwanami district only in 1847 by
Dairo Fujii in a report that did not become available until
1909 (91). Fujii found people, cattle, and horses affected by
wasting, abdominal swelling, and severe rashes on the legs,
but he did not know the cause. By the time Fujii's paper had
become available, another Japanese worker, Tokuho
Majima, had found schistosome eggs in pa tients with
Katayama disease (136, 172), and he associated the
pathological changes with the presence of the schistosome
eggs. The worm itself, S. japonicum, was discovered and de
penis discharging what has been interpreted as blood (69).
The juxtaposition is the papyri of aaa, antimony-based
remedies, and possibly worms in the body suggests
schistomiasis haematobia, and this interpretation is widely
quoted in historical and parasitological textbooks. How ever,
things are probably not as simple as this because no
passages from the papyri link aaa with the bladder or urine
and the discharge from the penis might represent semen
and not blood. This subject is discussed in more detail by
Nunn and Tapp (205), who abandon aaa as a possible
ancient Egyptian word for schistosomiasis. However, since
schistosomiasis was almost certainly common and
widespread in ancient Egypt, it is curious that the Egyptians
did not have a word for it unless it was so common that it
was ignored. In this context, it should be mentioned that
there have been a number of other suggestions about what
aaa might be, including hookworm disease, which is
discussed above.
If we accept that there is no authoritative description of
schistosomiasis in the earliest medical literature, the first de
finitive record must be that of an epidemic among soldiers in
Napoleon's army in Egypt in 1798 by a French army
surgeon, AJ Renoult, who writes that “A most stubborn
haematuria manifested itself amongst the soldiers of the
French army. . . con
scribed by Fujiro Katsurada in 1904 (134, 136), and its
devel opment in the snail host was described by Keinosuke
Miyairi and M. Suzuki in 1913 (136, 189), 2 years before
Leiper inde pendently described the life cycle of S.
haematobium. Fuller accounts of the history of Katayama
disease are given by Goodwin (101) and Grove (105).
The 20th century has been marked by the discovery of fur
ther species of schistosomes, S. intercalatum and S.
mekongi. The history of such an important disease as
schistosomiasis involves a great number of observations,
events, and individu als; a detailed account of the history is
given by Grove (105), and there are shorter accounts by
Foster (89), Goodwin (101), and Hoeppli (122). A full
bibliography is given by Warren (271), and an account of
schistosomiasis in the context of British and American
imperialism is given by Farley (77).
Liver and Lung Fluke Diseases
Over 100 other species of flukes infect humans either as
adults or as larvae, and only the most important ones are
considered here. These are Paragonimus westermani, the
lung fluke that causes paragonimiasis; Clonorchis sinensis,
the liver fluke that causes clonorchiasis; and Opisthorchis
spp., which cause opisthorchiasis. Virtually all the important
discoveries about the parasites themselves were made
during the period
1874 to 1918 as a result of observations on other parasitic
flukes such as Fasciola hepatica in sheep and others of
zoolog ical rather than medical interest. The life cycles of
these flukes are essentially similar to that described for
Schistosoma spp. above, with the added complication that
in some species, there is an additional intermediate host
between the snail and the human in or on which the
cercariae encyst. Humans become infected when they eat
the infected second intermediate host. The various
discoveries were made by a large number of peo ple, often
in obscure publications, and no attempt is made here to list
 the individual achievements; for this, the reader is re ferred
to Grove (105) and Muller (193). Our knowledge of the
pathologic effects of clonorchiasis and opisthorchiasis has
emerged gradually (111), with few historically interesting dis
coveries except the relatively recent finding of an
association with the bile duct cancer cholangiocarcinoma
(86).
The history of these infections as diseases begins with
the discovery of the worms and continues with the
elaboration of the life cycles. P. westermani was discovered
in the lungs of a human by Ringer in 1879 (193), and eggs
in the sputum were recognized independently by Manson
and Erwin von Baelz in 1880 (175, 193). Manson also
suggested that a snail might act as an intermediate host,
and a number of Japanese workers, including Koan
Nakagawa, Sadamu Yokogawa, Harujiro Kobayashi, and
Keinosuke Miyairi, reported on the whole life cycle in the
snail Semisulcospira between 1916 and 1922 (105).
The human liver fluke, C. sinensis, was first recognized
by James McConnell in 1875 (167, 136), and the snail host
was recognized by Masatomo Muto in 1918 (194, 136), but
it was the discovery in 1915 by Kobayashi of a second
intermediate host, an important food fish from which human
infections are acquired, that had the greatest impact on our
knowledge and control of this infection (139, 136).
The first records of Opisthorchis infections in humans
were made by Konstantin Wingradoff in 1892 (275), and the
602 COX CLIN. MICROBIOL. REV.
worms of humans, dogs, and other animals (257). Tyson
was the first person to recognize the “head” (scolex) of a
tape worm, and his subsequent descriptions of the anatomy
and physiology of the adult worms laid the foundations for
our knowledge of the biology of the taeniid tapeworms of
humans. Although by this time it had become clear that
there were differences between the broad tapeworm (see
below) and the other tapeworms that we now know to be
taeniids, the distinc tions between T. solium and T. saginata
were not obvious. These worms continued to be confused
long after the work of Tyson, and although Goeze (see
below) in 1782 had suspected that there were two species
(98), it was not until the middle of the 19th century that
Ku¨chenmeister is credited with recogniz ing the differences
between T. solium and T. saginata based on the
morphology of the scolex (144). In 1784, the first indica
tions that intermediate hosts were involved in the life cycles
of taeniid tapeworms emerged from the detailed studies of
the pork tapeworm by a German pastor, Johann August
Ephraim Goeze, who observed that the scolices of the
tapeworm in humans resembled cysts in the muscle of pigs
(99, 136). Some 70 years later, Ku¨chenmeister, in much-
criticized experiments, fed pig meat containing the cysticerci
of T. solium to criminals condemned to death and recovered
adult tapeworms from the intestine after they had been
executed (143, 145, 146). Shortly afterward, in 1868 to
1869, JH Oliver observed that T. saginata tapeworm
infections occurred in individuals who had eaten “measly”
beef (207), and this was confirmed by the Italian
veterinarian Edoardo Perroncito in 1877 (214).
The adult stages of T. solium and T. saginata rarely
cause any overt signs or symptoms, and there are no early
descriptions of diseases that might be caused by these
tapeworms. On the other hand, humans are host to two
important kinds of larval tapeworm, cysticerci of the pork
tapeworm T. solium and hy datid cysts of the dog tapeworm
Echinococcus granulosus. The encysted larvae, cystercerci,
snail and fish hosts and their roles in the life cycle were
discovered by Hans Vogel in 1934 (267).
Cestodiasis (Tapeworm Infections)
Humans can be infected by about 40 species of adult
tape worms and about 15 larval forms, mainly as accidental
hosts (9, 46). The most important cestodes belong to two
groups, the taeniid and diphyllobothriid tapeworms. The
characteristic taeniid adults, which can reach a length of
several meters, live in the intestine attached by a scolex
and shed mature proglot tids (“segments”) containing
numerous eggs, which pass out into soil or water, where the
eggs are released. When an in termediate host consumes
the eggs, they hatch in the intestine, releasing larval stages,
oncospheres, that burrow through the gut wall to reach
various tissues of the host, where they develop into
encysted cysticerci or bladderworms. The life cycle is com
pleted when undercooked or raw meat is eaten and the
cystic erci are released and attach to the gut wall of the final
host and develop into adult tapeworms. The two species in
humans, Taenia saginata, the beef tapeworm and the larger
of the two, and T. solium, the pork tapeworm, use cattle and
pigs as their respective intermediate hosts. The scientific
study of the tae niid tapeworms of humans can be traced to
the late 17th century and the observations of Edward Tyson
on the tape
of T. solium in the flesh of pigs, known as “measly pork,”
were well known to the ancient Greeks and are referred to
by Aristotle (384 to 322 BC), who, in the section on
diseases of pigs in his History of Animals, gives a detailed
and accurate account of “bladders that are like hailstones”
(202). Although the cysts in the muscle cause no obvious
illness in humans, cysts in the brain can cause symp toms
resembling epilepsy, and these must have been apparent in
early civilizations. However, there is nothing in the encyclo
pedic works of Hippocrates to suggest that the Greek physi
cians knew that humans harbored such cysts or suffered
from any conditions associated with them. There is,
however, indi rect evidence from different cultures that
people were aware of the possible dangers inherent in
eating the flesh of pigs. Ku¨chenmeister comments that
infections with cysticerci are not found in those, such as
Jews and Muslims, whose religious beliefs forbid the
consumption of pork (144), but as we have already seen,
similar arguments have been put forward with respect to
Trichinella spiralis infections. There are accounts of what
are possibly cysticerci in humans by Johannes Udalric
Rumler in 1558, Domenico Panaroli in 1652, and Thomas
Wharton in 1656, but none of these observers realized that
the structures they described were parasites (105). The first
reli able accounts of cystercerci as parasites of some kind
are by Philip Hartmann in 1688 (113, 136) and Marcello
(Marcus) Malpighi in 1697 (173), but the realization that
these cysts were
the larval stages of tapeworms had to await studies by
Johann Goeze in 1784 (99). The demonstration of the life
cycle of T. solium shed new light on the nature of the human
condition, cysticercosis, and it became apparent that
humans could prob ably become infected with the larval
stages of T. solium when they ingested the tapeworm eggs.
Although the conclusive ex periments could not be carried
out for ethical reasons, many experiments with animals and
observations of humans estab lished without doubt by the
 middle of the 19th century that cys ticercosis was caused by
the ingestion of the eggs of T. solium (145, 146). These
observations had a massive impact on the con trol of
tapeworm infections in humans by restricting the amount of
meat of infected animals available for human consumption.
There are brief accounts of the history of cysticercosis by
Nieto (202) and more detailed accounts by Foster (89) and
Grove (105). There are also less easily accessible accounts
by Vosgien (269), Henneberg (116), and Guccione (107).
The most serious human disease caused by a larval
cestode is echinococcosis, or hydatid disease, resulting
from accidental infection with larval stages of the canid
tapeworm, Echinococ cus granulosus, which frequently
occurs as an adult in dogs and as a larval cyst in wild and
domesticated animals including sheep. The massive
bladder-like hydatid cysts, particularly in the liver, were well
known in ancient times, and there are references to such
cysts in ritually slaughtered animals in the Babylonian
Talmud and, in animals slaughtered for food, by
Hippocrates in the fourth century BC, Arataeus in the first
century AD, and Galen in the second century AD (89, 105).
There are also descriptions of hydatid cysts in humans in
the Corpus Hippocratorum and in the works of Galen and in
later European medical texts, in which they have variously
been considered to be sacs of mucus, enlarged glands,
distorted blood vessels, lymphatic varices, or accumulations
of lymph (89, 144). Francisco Redi in the 17th century was
the first to appreciate the parasitic nature of these cysts
VOL. 15, 2002 HISTORY OF HUMAN PARASITOLOGY 603
already been mentioned, there was considerable confusion
with the two common species of Taenia. Nevertheless, by
the beginning of the 17th century, it became apparent that
there were two very different kinds of tapeworm (broad and
taeniid) in humans (105). It is generally agreed that
Diphyllobothrium was first recognized as being distinct from
Taenia by the Swiss physician Felix Plater, who also
provided the first descriptions of the disease at the
beginning of the 17th the century (217, 316). The first
accurate description of the proglottids was by another Swiss
biologist, Charles Bonnet, in 1750 (20, 136), but,
unfortunately, the worm he illustrated had a Taenia scolex,
a mistake he remedied in 1777 (21, 136). By the middle of
the 18th century, it was apparent that infections with D.
latum occurred in humans whose diet was mainly fish.
However, it was not until the life cycles of other tapeworms
of zoological interest had been elaborated that further
progress became possible, since the existence of three
hosts in the life cycle, human, fish, and copepod, confused
the issue. An understand ing of the life cycle of this parasite
began in 1790, when the Dane Peter Christian Abildgaard
observed that the intestine of sticklebacks contained worms
that resembled the tapeworms found in fish-eating birds (1,
136); however, it was some time before there was any
significant advance in our understanding of the life cycle of
D. latum. In the meantime, there were a number of
misleading observations until 1881, when the Ger man
zoologist Maximillian Gustav Christian Carl Braun real ized
that the unsegmented tapeworms common in pike and other
fish were the larval stages of D. latum and succeeded in
infecting dogs with these plerocercoids; in 1882 he achieved
similar results in humans (23, 136). Braun suspected that
this was not the whole story, but it was many years later that
two Polish scientists, Constantine Janicki and Felix Rosen,
working in Switzerland, incriminated copepods in the life
cycle and showed that they fed on the eggs of the tapeworm
(136, 223), but credit for the hypothesis that these cysts
were the larval stages of tapeworms goes to the German
clinician and natural histo rian Pierre Simon Pallas, who
showed this in 1766 (136, 212). It was not until 1853 that
Carl von Siebold demonstrated that Echinococcus cysts
from sheep gave rise to adult tapeworms when fed to dogs
(268), and in 1863 Bernhard Naunyn found adult tapeworms
in dogs fed with hydatid cysts from a human (198, 136).
There are good accounts of the history of hydatid disease
by Foster (89) and Grove (105).
Humans also harbor the adults of Diphyllobothrium latum,
the broad or fish tapeworm that lives in the intestine. Eggs
are passed out in the feces, and the first larval stage, the
coracid ium, develops within the egg and is eaten by a
copepod, in which it develops to the second larval stage,
the procercoid. When an infected copepod is eaten by a
fish, the procercoid develops into the third larval stage, the
plerocercoid, and when a human eats an infected fish, the
plerocercoid develops into an adult tapeworm in the gut.
The broad tapeworm was well known in antiquity and is
mentioned, sometimes indirectly, in the major classical
medical writings including the Ebers papy rus, the Corpus
Hippocratorum, and the works of Celsus and Avicenna.
However, there are no accurate early clinical records
because there are few overt signs of the infection apart from
abnormal hunger, malaise, and abdominal pain. Early
descriptions of the worm tend to be unreliable because, as
has
and were then eaten by fish, which, in their turn, were eaten
by humans (129, 136). There are good accounts of
Dipyllobothrium and diphyllobothriasis by Foster (89) and
Grove (105).
DISCOVERY OF THE PARASITIC PROTOZOA
Because of their small size, it was not possible to
recognize any protozoa until the invention of the microscope
and its use by Antonie van Leeuwenhoek toward the end of
the 17th century. The study of parasitic protozoa only really
began two centuries later, following the discovery of
bacteria and the promulgation of the germ theory by
Pasteur and his colleagues at the end of the 19th century.
Amoebae and Amoebiasis
Humans harbor nine species of intestinal amoebae, of
which only one, Entamoeba histolytica, is a pathogen. The
life cycle is simple. The amoebae live and multiply in the gut
and form cysts that are passed out in the feces and infect
new individuals when they are consumed in contaminated
water or food. Most infections are asymptomatic, but some
strains of E. histolytica can invade the gut wall, causing
severe ulceration and amoebic dysentery characterized by
bloody stools. If the parasites gain access to damaged
blood vessels, they may be carried to ex traintestinal sites
anywhere in the body, the most important of
which is the liver, where the amoebae cause hepatic
amoebi asis. Supposed evidence that both the intestinal and
liver forms of the disease were recognized from the earliest
times is cir cumstantial because there are so many causes
of both the bloody dysentery characteristic of amoebiasis
and the symp toms of hepatic amoebiasis that many of
these records are open to other interpretations (24). With
these reservations in mind, the earliest record is possibly
 that from the Sanskrit document Brigu-samhita, written
about 1000 BC, which refers to bloody, mucose diarrhea
(260). Assyrian and Babylonian texts from the Library of
King Ashurbanipal refer to blood in the feces, suggesting
the presence of amoebiasis in the Tigris Euphrates basin
before the sixth century BC (24, 148), and it is possible that
the hepatic and perianal abscesses described in both
Epidemics and Aphorisms in the Corpus Hippocratorum
refer to amoebiasis (131). Since epidemics of dysentery by
itself are likely to result from bacterial infections and
dysentery associated with disease of the liver is likely to be
amoebic, later records are easier to interpret. In the second
century AD, Galen and Celsus both described liver
abscesses that were probably amoebic, and the works of
Aretaeus, Archigenes, Aurelanus, and Avicenna toward the
end of the first millen nium give good accounts of both
dysentery and hepatic in volvement (238). As amoebiasis
became widespread in the developed world, there were
numerous records of “bloody flux” in Europe, Asia, Persia,
and Greece in the Middle Ages (137). The disease appears
to have been introduced into the New World by Europeans
sometime in the 16th century (51), and with the later
development of European colonies and increased world
trade, there are numerous clear descriptions of both the
intestinal and hepatic forms of amoebiasis. In the 19th
century, several books mainly concerned with diseases in
India, including Researches into the Causes, Nature and
Treat ment of the More Prevalent Diseases of India and of
Warm Climates Generally by James Annersley, clearly refer
604 COX CLIN. MICROBIOL. REV.
was more than one species in humans came from the work
of Heinrich Iranaus Quincke and Ernst Roos working in Kiel
in 1894, who observed that cats could only be infected per
rectum or orally with cysts of amoebae that contained
ingested red blood cells and not with those that did not, ie,
E. coli (220, 227). Thereafter, the most contentious
arguments relate to the various morphologically identical
species and strains of E. his toloytica, and their relationship
to disease has only recently been resolved by using
biochemical techniques that clearly show that the presence
of two common species, E. histolytica, which can cause
disease, and E. dispar, which cannot (237).
The history of amoebiasis is well documented. The most
comprehensive account of the early history is that by Dobell
(60), and there are also good accounts of the early history
by Bray (24), Foster (89), Kean (135), Scott, (238), and
Wenyon (272) and reviews containing more recent
information by Craig (50), Guirola (110), Imperato (127),
Mart´ınez-Ba´ez, (184), Stilwell (248), and Svanidtse (249).
Giardia and Giardiasis
Giardia holds a special place in the science of parasitic
protozoology because the parasite Giardia duodenalis, also
known as G. lamblia or G. intestinalis, was the first parasitic
protozoan of humans seen by Antonie van Leeuwenhoek in
1681 (62, 136). The life cycle of Giardia is very simple: the
parasites multiply in the duodenum and form cysts that are
passed out in the feces and infect new individuals when
they are swallowed in food or water. Most infected
individuals show few or no signs of infection, but in some,
particularly children, there may be malabsorbtion, diarrhea,
and abdominal pain. G. duodenalis was first seen by
Leeuwenhoek and, interestingly, associated by him with his
own loose stools. Leeuwenhoek's illustrations are not very
to both intestinal and hepatic amoebiasis (6), and it is now
generally agreed that this book contains the first accurate
descriptions of both forms of the disease. The connection
between amoebic dysentery and liver abscesses was
described by William Budd, the English physician who
discovered the method of transmis sion of typhoid (30). The
amoeba itself, E. histolytica, was discovered by Friedrich
Lo¨sch (also known as Fedor Lesh) in 1873 in Russia (163),
and Lo¨sch also established the relation ship between the
parasite and the disease in dogs experimen tally infected
with amoebae from humans. Stephanos Kartulis, a Greek
physician, also found amoebae in intestinal ulcers in
patients suffering from dysentery in Egypt in 1885 and 1896
and noted that he never found amoebae from nondysenteric
cases (132). Kartulis also showed that cats could be
infected with amoebae per rectum and developed dysentery
(133) a finding discussed below. The authoritative report by
William Thomas Councilman and Henri Lafleur, working at
the Johns Hopkins Hospital in 1891, represents a definitive
statement of what was known about the pathology of
amoebiasis at the end of the 19th century, and much of it is
still valid today (47).
It was pointed out above that humans harbor several
species of amoebae. The most common are E. histolytica,
which has just been considered, and a larger and
superficially similar harmless species, E. coli; the presence
of these two parasites confused early workers in this field.
The first clues that there
informative, and the first good illus trations of Giardia are
those of Vile´m Lambl in 1859 (136, 150). The parasite
received little attention until 1902, when the American
parasitologist Charles Wardell Stiles began to sus pect that
there was a causal relationship with diarrhea (247). This
was not followed up until the 1914 to 1918 World War, when
soldiers with diarrhea were found to pass Giardia cysts that
caused similar symptoms when administered to laboratory
animals (75). In 1921, Clifford Dobell suggested that Giardia
was a pathogen (61), and in 1926, Reginald Miller, a
physician working in London, conclusively showed that
some children infected with Giardia did suffer from
malabsorption whereas others acted as unaffected carriers
(188). It was not until 1954, however, that the detailed
studies by the American physician Robert Rendtorff
produced unambiguous evidence linking the parasite with
the disease (224). In the 300 years since Giardia was first
discovered, it has become recognized as a common
parasite and potential pathogen worldwide; however, it is
still not known how many species infect humans and what
role, if any, reservoir hosts play in the epidemiology of the
infection. Fuller accounts of the history of giardiasis are
given by Wen yon (272) and Farthing (78).
African Trypanosomes and Sleeping Sickness
African trypanosomiasis is caused by infection with two
sub species of trypanosomes, Trypanosoma brucei
gambiense, which
causes Gambian or chronic sleeping sickness, and T. b.
rhod esiense, which causes Rhodesian or acute sleeping
sickness. The trypanosomes multiply in the blood and are
taken up by tsetse flies when they feed. Within the tsetse fly,
there is a phase of multiplication and development resulting
in the for mation of infective trypanosomes in the salivary
 glands of the fly, which are injected into a new host when
the fly feeds. The infection itself causes a number of
symptoms including anemia, wasting and lethargy, and, in
some cases, if the para sites pass into the brain and
cerebrospinal fluid, coma and death. There are similar
parasites in wild and domesticated animals. The first
definitive accounts of sleeping sickness are by an English
naval surgeon, John Atkins, in 1721 (10) and Thomas
Winterbottom, who coined the term “negro lethargy” in 1803
(276). An appreciation of the real cause of the disease was
not possible until Pasteur had established the germ theory
toward the end of the 19th century. Trypanosomes had
been seen in the blood of fishes, frogs, and mammals from
1843 onward, but it was not until 1881 that Griffith Evans
found trypanosomes in the blood of horses and camels with
a wasting disease called surra and suggested that the
parasites might be the cause of this disease (74). These
observations led to the most important discoveries about
human and animal trypano somiasis shortly afterwards. In
1894, David Bruce, a British army surgeon investigating an
outbreak of nagana, a disease similar to surra, in cattle in
Zululand, was looking for a bac terial cause and found
trypanosomes in the blood of diseased cattle; he
demonstrated experimentally that these caused na gana in
cattle and horses and also infected dogs. He also observed
that infected cattle had spent some time in the fly infested
“tsetse belt” and that the disease was similar to that in
humans with negro lethargy and fly disease of hunters (26).
Trypanosomes were seen in human blood by Gustave
Nepveu in 1891 (200). In 1902, Everett Dutton identified the
VOL. 15, 2002 HISTORY OF HUMAN PARASITOLOGY 605
bugs because of their tendency to bite the lips and face.
The transient trypanosome forms circulate in the blood and
are taken up by a blood-sucking bug when it feeds. The
parasites multiply in the gut of the bug, and infective forms
are passed out in the feces while the bug is feeding on a
new host and are rubbed into the bite. In the human host,
parasites enter and multiply in a variety of different cells and
eventually induce what are thought to be autoimmune
responses that results in the destruction of both infected
and uninfected tissues. The nature of the disease depends
on the tissues and organs in volved, and the most
conspicuous forms are massive distension of the intestinal
tract, especially the esophagus and colon, and destruction
of cardiac muscle, which can result in death many years
after the initial infection. T. cruzi infections are common in
many mammals on the American continent, but the human
disease now occurs only in South and Central America. The
earliest indication that Chagas' disease is an ancient
infection in South America comes from the examination of
spontane ously mummified human remains from Chile
between 470 BC and AD 600 that show clear signs of the
characteristic destruc tive nature of the disease (233). The
use of immunological and molecular techniques has made it
possible to detect the pres ence of T. cruzi without
necessarily visualizing the parasites themselves. T. cruzi
DNA has been detected in the heart and esophagus of
mummified bodies from Peru and northern Chile dating from
2000 BC to AD 1400 (109) and in samples from bodies in
museums from northern Chile from about AD 1000 to 1400
(85). The parasites themselves have also been identi fied
by light and electron microscopy in a Peruvian mummy from
the 15 to 16th century AD (88).
The history of T. cruzi and Chagas' disease really begins
with a series of discoveries by the Brazilian scientist Carlos
trypano some that causes Gambian or chronic sleeping
sickness (T. b. gambiense) in humans (68), and in 1910
JWW Stephens and Harold Fantham described T. b.
rhodesiense, the cause of Rho desian or acute sleeping
sickness (136, 246). Although Bruce had shown that
trypanosome infections in cattle were acquired from tsetse
flies, he thought that transmission was purely me chanical,
and the role of the tsetse fly in the transmission of sleeping
sickness remained controversial until Friedrich Kleine, a
colleague of Robert Koch, demonstrated in 1909 the
essential role of the tsetse fly in the life cycle of
trypanosomes (138).
The persistence of trypanosomes in the blood and the
exis tence of successive waves of parasitemia were
described in detail by Ronald Ross and David Thompson in
1911 (232), but the actual mechanism of what happens and
how the parasite evades the immune response, now called
antigenic variation, was not elaborated until the work of
Keith Vickerman in 1969 (265). The story of African
sleeping sickness is told briefly by Hoare (119) and in more
detail by Foster (89), Nash (196), Lyons (166), Wenyon
(272), and Williams (274).
South American Trypanosomiasis: Chagas' Disease
Chagas' disease is caused by infection with another
trypano some, Trypanosoma cruzi, transmitted by insects
belonging to the order Hemiptera or true bugs, commonly
known as kissing
Chagas, between 1907 and 1912. Chagas not only
discovered the try panosome T. cruzi and demonstrated its
transmission by bugs but also described the disease that
affects some 18 million people and now commemorates his
name. Chagas' first obser vation was that the blood-sucking
bugs that infested the poorly constructed houses harbored
flagellated protozoa and that when these flagellates were
injected into monkeys and guinea pigs, trypanosomes
appeared in the blood (39, 136). Chagas later found the
same trypanosomes in the blood of children with an acute
febrile condition and suspected that blood-suck ing bugs
might also transmit the parasite to humans, but he thought
that the trypanosomes were transmitted via the bite of the
insect (40, 41). It was the French parasitologist Emile
Brumpt who demonstrated transmission via the fecal route
(28, 136). The links between infection with T. cruzi and the
various signs of Chagas' disease, such as distended colon
and esopha gus and cardiac failure, were not determined
until the work of Fritz Koberle in the 1960s (140). Exactly
how the damage to heart and nerves is caused and what
role the autoimmune component plays are still controversial.
The history of Chagas' disease has been well documented
by Scott (238), Lewinsohn (158), Leonard (156), Miles
(187), and Wenyon (272).
Leishmania and Leishmaniasis
Leishmaniasis, caused by several species of Leishmania,
is transmitted by sandflies and occurs in various forms in
the Old and New World. The parasites infect and multiply in
macro
phages and are taken up by sandflies when they feed. In
the gut of the sandfly, the parasites multiply and reach the
mouthparts, from where they are injected into a new host
 when the sandfly feeds again. The disease, leishmaniasis,
takes a number of forms ranging from simple cutaneous
ulcers to massive de struction of cutaneous and
subcutaneous tissues in the muco cutaneous forms and the
involvement of the liver and other organs in the visceral
form.
From a historical viewpoint, it is easiest to consider the
Old World forms first. Old World cutaneous leishmaniasis,
known as oriental sore, is an ancient disease, and there are
descrip tions of the conspicuous lesions on tablets in the
library of King Ashurbanipal from the 7th century BC, some
of which are thought to have been derived from earlier texts
from 1500 to 2500 BC (183). There are detailed
descriptions of oriental sore by Arab physicians including
Avicenna in the 10th century, who described what was (and
is) called Balkh sore from north ern Afghanistan, and there
are later records from various places in the Middle East
including Baghdad and Jericho; many of the conditions
were given local names by which they are still known (183).
Old World visceral leishmaniasis, or kala azar,
characterized by discolored skin, fever, and enlarged
spleen, is easily confused with other diseases, especially
ma laria. Kala azar was first noticed in Jessore in India in
1824, when patients suffering from fevers that were thought
to be due to malaria failed to respond to quinine; by 1862
the disease had spread to Burdwan, where it reached
epidemic propor tions (71). The cause remained unknown,
and several eminent clinicians, including Ronald Ross, were
convinced that kala azar was a virulent form of malaria
(230). It was not until the parasite, L. donovani, was
discovered in 1900 by Leishman and Donovan (see below)
606 COX CLIN. MICROBIOL. REV.
sculptures since the 5th century and in the writings of the
Spanish missionaries in the 16th century (149). It was
originally thought that New World Leishmaniasis and Old
World leish maniasis were the same, but in 1911 Gaspar
Vianna found that the parasites in South America differed
from those in Africa and India and created a new species,
Leishmania braziliensis (264). Since then, a number of other
species unique to the New World have been described.
Following the discovery of the sandfly transmission of Old
World leishmaniasis, the vectors in the New World were
also assumed to belong to the genus Phlebotomus, but in
1922 it was discovered that the genus involved was actually
Lutzomyia. Over the last two decades, the complex pattern
of species of parasite, vector, reservoir host, and disease
has been painstakingly elaborated by Ralph Lain son and
his colleagues (149).
Malaria
Malaria is one of the most important infectious diseases
in the world, and its history extends into antiquity. The
disease is caused by four species of the genus
Plasmodium, P. falciparum, P. vivax, P. ovale, and P.
malariae. Similar parasites are com mon in monkeys and
apes. It is now generally held that malaria arose in our
primate ancestors in Africa and evolved with humans,
spreading with human migrations first throughout the
tropics, subtropics, and temperate regions of the Old World
and then to the New World with explorers, missionaries, and
slaves. The characteristic periodic fevers of malaria are re
corded from every civilized society from China in 2700 BC
through the writings of Greek, Roman, Assyrian, Indian, Ar
abic, and European physicians up to the 19th century. The
earliest detailed accounts are those of Hippocrates in the
that the true nature of the disease be came apparent (118).
The discovery of the parasites responsible for the Old
World cutaneous disease is controversial, and a number of
observers described structures that might or might not have
been leish manial parasites from oriental sores (272). Credit
for their discovery is usually given to an American, James
Homer Wright (136, 279), although there is no doubt that
they were actually seen in 1885 by David Cunningham (52,
136), who did not realize what they were, and in 1898 by a
Russian military surgeon, PF Borovsky (118, 136). The
discovery of the par asite that causes visceral
leishmaniasis, L. donovani, is less controversial, and it is
universally accepted that a Scottish army doctor, William
Leishman (136, 155), and the Professor of Physiology at
Madras University, Charles Donovan (64, 136),
independently discovered the parasite in the spleens of pa
tients with kala azar. It is fair to point out that Borovsky's
discoveries were unknown to Wright and to Leishman and
Donovan.
The search for a vector was a long one, and it was not
until 1921 that the experimental proof of transmission to
humans by sandflies belonging to the genus Phlebotomus
was demon strated by the Sergent brothers, Edouard and
Etienne (239). The actual mode of infection, through the bite
of the sandfly, was not finally demonstrated until 1941 (4,
136). The history of Old World leishmaniasis is described by
Garnham (96), Man son-Bahr (183), and Wenyon (272).
In the New World, cutaneous and mucocutaneous
leishman iasis cause disfiguring conditions that have been
recognized in
5th century BC, and thereafter there are increasing numbers
of references to the disease in Greece and Italy and
throughout the Roman Empire as its occurrence became
commonplace in Europe and elsewhere. Over this period, it
became clear that malaria was associated with marshes,
and there were many ingenious explanations to explain the
disease in terms of the miasmas rising from the swamps
(112).
Our scientific understanding of malaria did not begin until
the end of the 19th century following the establishment of
the germ theory and the birth of microbiology, when it
became necessary to discover the cause of the disease that
was then threatening many parts of the European empires.
The discov ery of the malaria parasite and its mode of
transmission are among the most exciting events in the
history of infectious diseases, and this topic has been
reviewed many times, partic ularly by Bruce-Chwatt (27),
Garnham (94), Harrison (112), McGregor (170), Poser and
Bruyn (218), and Wenyon (273).
The life cycle is a very complex one that begins when an
infected anopheline mosquito injects sporozoites, the infec
tious stages, into the blood of its host. Sporozoites enter
and multiply in liver cells, and thousands of daughter forms,
mero zoites, are released into the blood. These merozoites
invade red blood cells, in which another phase of
multiplication oc curs; this process is repeated indefinitely,
causing the symp toms of the disease we call malaria.
Some merozoites do not divide but develop into sexual
stages, the male and female gametocytes, that are taken up
by another mosquito when it feeds; fertilization and zygote
formation occur in the gut of the mosquito. The zygote
develops into an oocyst on the outside of
the mosquito gut, and within the oocyst there is another
 phase of multiplication that results in the production of
sporozoites that reach the salivary glands to be injected into
a new host. The parasites in the blood were first seen in
1880 by a French army surgeon, Alphonse Laveran, who
was looking for a bac terial cause of malaria and who
immediately realized that the parasites were responsible for
the disease (152).
The discovery that the mosquito acted as a vector was
due to the intuition of Patrick Manson. Manson had already
demon strated that filarial worms, also blood parasites, were
transmit ted by mosquitoes and postulated that the vector of
the malaria parasite might also be a mosquito, partly
because of his knowl edge of the life cycle of filarial worms
and partly because of the known association between the
disease and marshy places in which mosquitoes breed
(178). Manson was unable to under take this investigation
himself and persuaded Ronald Ross, an army surgeon, to
carry out the work in India. The story of Ross' discoveries
has been told many times and is not repeated in detail here,
since there are excellent accounts by Ross himself (231)
and in the Ross-Manson collected letters (34) and also by
Bruce-Chwatt (27), Garnham (94), Harrison (112), Manson
Bahr (182), Nye and Gibson (206), Poser and Bruyn (218),
and Russell (236). In 1897, Ross saw what we now know to
be the oocysts of P. falciparum in an anopheline mosquito
that had fed on a patient with crescentic malaria parasites
(gameto cytes) in his blood, but he was unable to follow this
up at the time (228). Turning his attention to a bird malaria,
P. relictum, he found all the stages of the parasite in culicine
mosquitoes that had fed on infected sparrows (136, 229). In
making this discovery, Ross acknowledged the work of a
young Canadian, William George MacCullum, whose
VOL. 15, 2002 HISTORY OF HUMAN PARASITOLOGY 607
majority of cases, infections are asymptomatic; however, it
can be a serious cause of mortality and morbidity in fetuses
and immunodeficient individuals. The parasite that causes
the in fection, Toxoplasma gondii, was discovered
independently by the French parasitologists Charles Nicolle
and Louis Herbert Manceaux while looking for a reservoir
host of Leishmania in a North African rodent, the gundi
Ctenodactylus gondi (136, 201) and by Alfonso Splendore
in Sao Paulo in rabbits (136, 245). At about the same time,
Samuel Taylor Darling saw what were probably similar
organisms in a human (53), and the first definitive
observation of T. gondii from a child in connection with an
infection was made by a Czech physician, Josef Janku, in
1923 (130). Even then, T. gondii was largely regarded as an
interesting curiosity until an association with human
congenital disease was recognized in 1937 by Arne Wolf
and David Co wen (277). This association was followed by
the realization that T. gondii rarely causes disease even
though it is a very common parasite of adults but that in
pregnant women the parasite can cross the placenta and
can damage the fetus. The early history of the discovery of
T. gondii and toxoplasmosis is discussed by Wenyon (273)
and Dubey and Beattie (65).
While these developments were taking place, there were
increasing numbers of records from virtually all species of
mammals and many birds, but the nature of the parasite re
mained obscure until the life cycle had been worked out.
The life cycle of T. gondii is a very complicated one and
remained elusive until 1970, when scientists in Britain,
Germany, The Netherlands, and the United States
independently demon strated that this parasite was a stage
in the life cycle of a common intestinal coccidian of cats. In
studies on the develop ment of the sexual stages of a
related avian parasite Hal teridium ( Haemoproteus)
columbae had led him to the con clusion that these
parasites were similar to those in the blood of humans with
malaria (168, 136). In the same year that Ross made his
discovery, the Italian malariologists Giovanni Battista
Grassi, Amico Bignami, and Giuseppe Bastianelli described
the developmental stages of malaria parasites in anopheline
mosquitoes; the life cycles of P. falciparum, P. vivax, and P.
malariae were described a year later (103). For nearly 50
years, the life cycle in humans remained incompletely
understood and nobody knew where the parasites, which
could not be seen in the blood, developed during the first 10
days after infection. In 1947, Henry Shortt and Cyril
Garnham, working in London, showed that a phase of
division in the liver preceded the development of parasites
in the blood (242). The final brick was put in place when an
American clinician, Wojciech Kro toski, in collaboration with
Garnham's team, showed that in some strains of P. vivax
the stages in the liver could remain dormant for several
months (142). Sadly, the discovery of the life cycle of the
malaria parasite eventually led to acrimony between Ross
and Manson and between the British and the Italians,
something that still rumbles on a century later (56, 63, 76).
Toxoplasma, Toxoplasmosis, and Infections
Caused by Related Organisms
Toxoplasmosis is one of the most common and
widespread parasitic infections but is relatively little known
because in the
the most simple form of the life cycle, cats become infected
when they swallow oo cysts, the resistant infective stages
containing sporozoites, which invade and multiply in
intestinal cells, where sexual stages are produced,
fertilization occurs, and oocysts are pro duced. However,
there is an alternative life cycle. If the oocysts are
swallowed by a mouse (or any other nonfeline host), mul
tiplication occurs in the intestinal cells, but instead of sexual
stages being produced there follows a disseminated
infection during which resistant stages form in the brain and
muscle. There is no further development in the mouse, but
when the mouse is eaten by a cat, the life cycle reverts to its
basic sexual pattern. Humans are infected in the same way
as mice if they consume oocysts, but they can also become
infected by eating any kind of meat containing the resistant
forms. It is therefore not surprising that the life cycle
remained elusive until William McPhee Hutchison, working
in Glasgow in 1965, showed that the infectious agent was
passed in the feces of cats. At the time he thought that it
was transmitted with a nematode worm, as happens with
the flagellate Histomonas meleagridis and the nematode
Heterakis gallinarum in fowl. Hutchison subse quently
identified protozoan cysts in the feces as those of a
coccidian related to Isospora, a common parasite of cats
(125, 126). In the meantime, other groups were following up
Hutchi son's 1965 observation of the presence of infectious
agents in the feces of cats, and Hutchison's incrimination of
the isospo ran parasite of cats as T. gondii was
independently confirmed by Jack Frenkel (90) and Harley
Sheffield (241) in the United States, Gerhard Piekarski in
Germany (216), and JP Over dulve in The Netherlands
(210). The discovery of the T. gondii life cycle initiated a
massive search for similar phases in the life
cycles of other coccidian parasites, with the result that a
num ber of protozoa that had not been properly identified
were classified as stages in the life cycle of other poorly
understood coccidians and that in many cases transmission
depended on a predator-prey relationship (250). Humans
are infected with two related parasites, Sarcocystis hominis
and S. suihominis, acquired from beef and pork,
respectively, and S. lindemanni, whose source is unknown.
The early history of our knowledge of Sarcocystis is covered
by Wenyon (273), and subsequent discoveries are
described by Tadros and Laarman (250).
Humans are also hosts to three other species of coccidia,
Isospora belli, Cryptosporidium parvum, and Cyclospora
cayet anensis, that have in the past been regarded as rare
and acci dental curiosities but have recently been identified
as patho gens in AIDS patients and other
immunocompromised individuals. All have simple life cycles
initiated by the ingestion of oocysts followed by
multiplication and spread within the intestinal cells of the
host and the eventual production of sexual stages, as for T.
gondii infection in cats. C. parvum was discovered in 1912
by the American parasitologist Edward Ernest Tyzzer in the
gastric glands of laboratory mice in which he had previously
found another species, C. muris (259). C. parvum is not very
host specific, and the first cases in humans were recorded in
1976 independently by Nime (203) and Meisel (186). From
1981 onward, numerous new cases began to be recognized
in AIDS patients. The oocysts Cryptospo ridium are very
resistant to chlorination, and the source of these infections is
probably drinking water contaminated with cattle feces.
Cryptosporidium infections are now known to be very
common and have caused a number of epidemics in which
608 COX CLIN. MICROBIOL. REV.
myxosporidians are more closely related to the Metazoa
than the Protozoa and that the microsporidians are more
closely related to the Fungi (38). Nevertheless,
microsporidians are still regarded as the province of
parasitologists and have be come important as concomitant
infections in AIDS patients. The life cycle of microsporidians
is quite complex. The most conspicuous stage is the
resistant gram-positive spore contain ing a coiled filament
and an infective body, the sporoplasm. The host becomes
infected when the spore is ingested or in haled. The
sporoplasm is extruded through the filament and penetrates
a host cell, within which the organism multiplies and spreads
to other cells; eventually, another generation of spores is
produced. There are, however, many variations on this
basic pattern. What are now thought to have been the
spores of Nosma bombycis were described by Na¨geli
investi gating an outbreak of a disease called pe´brine in the
silkworm Bombyx mori in 1857 (195) and studied in much
more detail by Louis Pasteur in 1865 to 1870 (261). During
the 19th century, microsporidians attracted considerable
attention mainly as parasites of invertebrates. Our
knowledge of human micros poridiosis in the past is limited
because of difficulties in inter preting various structures that
might or might not have been spores, but from the second
decade of the 20th century on ward, there have been a
number of sporadic reports of what might have been human
microsporidial infections. The first case was probably that of
Encephalitozoon chagasi in a new born baby recorded in
1927 (255), but the first authenticated record was not until
1959, when Hisakichi Matsubayashi and his colleagues in
Japan found an Encephalitozoon sp. in boy with convulsions
the victims have experienced abdominal pain and diarrhea.
In immunodepressed individuals, especially those infected
with HIV, the infection can become disseminated to the liver,
pan creas, and respiratory tract and can be fatal. There is an
ex cellent history of human cryptosporidiosis by McDonald
(169) and a short but useful review by Dubey et al. (66).
C. cayetanensis is another coccidian that is associated
mainly with AIDS. In 1979, the English parasitologist
Richard Ash ford found an unidentified coccidian in patients
in Papua New Guinea (8), but it received little attention until
it was found again in the stools of patients with HIV by
Soave et al. in 1986 (243). In 1992, this parasite was named
Cyclospora cayetanensis (209), and since then it has been
identified as the cause of a number of outbreaks of diarrhea
and fatigue in both immuno competent and
immunosuppressed individuals (108). Cyclo spora infections
are known to be transmitted in water and on fruit, but the
original source is not known.
The last of this group of parasites, Isospora belli,
discovered by Woodcock in 1915 (278), is another coccidian
frequently found in asymptomatic immunocompetent
individuals but as sociated with diarrhea in AIDS patients.
The whole subject of parasitic infections in
immunocompromised hosts is discussed by Ambroise-
Thomas (5).
Microsporidians
Microsporidians are extemely common spore-forming
para sites of vertebrates and invertebrates that were until
relatively recently grouped with myxosporidians as
cnidosporidians and classified with or close to the
Sporozoa. We now know that the
(185). Thereafter, there were reports of a number of
sporadic cases of microsporidian infections in hu mans (38),
but interest in this group really took off in 1988, when E.
bieneusi was found in an AIDS patient (58). Since then,
about 7 genera and 14 species associated with fulminat ing
infections in immunodepressed patients and less serious
infections in immunocompetent individuals have been de
scribed (36, 37) and the number of cases, particularly in
AIDS patients, continues to rise (5). Despite their
importance, very little is known about the transmission and
epidemiology of the microsporidians.
SUMMARY AND CONCLUSIONS
The history of parasitology is a fascinating one, and
parasites have been the subjects of some of the most
exciting discoveries in the field of infectious diseases. We
now know that many of the important parasites encountered
today not only existed but were widespread in their
distribution before written records began, and our early
ancestors must have been aware of the presence of the
largest and most common worms and of some of the
diseases caused by parasites. The subsequent history of
human parasitology revolves around early descriptions of a
particular disease and the identification of the parasite
causing the disease, not necessarily in this order; the
elaboration of the life cycle; and, finally, the establishment of
the causal relation ship between the parasite and the
disease. In this review, it has been possible only to touch on
the major events and some of the personalities involved in
these discoveries, but the history of parasitology has been
well served in the scientific literature and the interested
reader is referred to the appropriate sec
tions in books that are concerned mainly with aspects of
med icine, particularly tropical medicine, such as those by
Ack ernecht (2), Brothwell and Sandison (25), Bynum and
Porter (35), Chernin (42), Cox (48), Kiple (137), Mack (171),
Norman (204), Ranger and Slack (221), Ransford (222),
and Scott (238). There are also a number of publications
dedicated to the history of parasitology, including those by
Cox (49), Foster (89), Garnham (95), Hoeppli (120, 121),
and Warboys (270). The most comprehensive work on the
history of any aspect of parasitology is A History of Human
Helminthology (105), which contains over 800 pages of
detailed accounts of all the discov eries in the field of
human helminthology. The two-volume Tropical Medicine
and Parasitology: Classical Investigations ed ited by Kean
et al. (136) requires a special mention, since it is an
invaluable source of information consisting of whole arti
cles, excerpts, and translations of most of the important
papers in the history of parasitology.
ACKNOWLEDGMENTS
This study was carried out while I was in receipt of a Leverhulme
Trust Emeritus Fellowship, and I am grateful to the Trust for its
support. I also thank the London School of Hygiene and Tropical
Medicine for accommodating me as a Senior Visiting Research
Fellow.
This work would not have been possible without the help and en
couragement I received from a number of libraries, particularly
those of the London School of Hygiene and Tropical Medicine, the
Well come Trust, and the Royal College of Physicians, and from
colleagues too numerous to mention individually.
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